Download Chapter 10.qxp

The 2% Difference
Now that scientists have decoded the chimpanzee
genome, we know that 98 percent of our DNA
is the same. So how can we be so different?
BY ROBERT SAPOLSKY
printout, march through the two genomes, and see
exactly where our 2 percent difference lies.
f you find yourself sitting close to a chimpanzee,
staring face to face and making sustained eye contact, something interesting happens, something that
is alternately moving, bewildering, and kind of
creepy, When you gaze at this beast, you suddenly
realize that the face gazing back is that of a sentient
individual, one who is recognizably kin. You can’t
help but wonder, What’s the matter with those intelligent design people?
I
Given the outward differences, it seems reasonable to expect to find fundamental differences in
the portions of the genome that determine chimp
and human brains—reasonable, at least, to a brainocentric neurobiologist like me. But as it turns out,
the chimp brain and the human brain differ hardly at
all in their genetic underpinnings. Indeed, a close
look at the chimp genome reveals an important lesson in how genes and evolution work, and it suggests that chimps and humans are a lot more similar
than even a neurobiologist might think.
Chimpanzees are close relatives to humans, but
they’re not identical to us. We are not chimps.
Chimps excel at climbing trees, but we beat them
hands down at balance-beam routines; they are covered in hair, while we have only the occasional guy
with really hairy shoulders. The core differences,
however, arise from how we use our brains. Chimps
have complex social lives, play power politics,
betray and murder each other, make tools, and teach
tool use across generations in a way that qualifies as
culture. They can even learn to do logic operations
with symbols, and they have a relative sense of
numbers. Yet those behaviors don’t remotely
approach the complexity and nuance of human
behaviors, and in my opinion there’s not the tiniest
bit of scientific evidence that chimps have aesthetics, spirituality, or a capacity for irony or poignancy.
NA, or deoxyribonucleic acid, is made up of
just four molecules, called nucleotides: adenine
(A), cytosine (C), guanine (G), and thymine (T).
The DNA codebook for every species consists of
billions of these letters in a precise order. If, when
DNA is being copied in a sperm or an egg, a
nucleotide is mistakenly copied wrong, the result is
a mutation. If the mutation persists from generation
to generation, it becomes a DNA difference—one of
the many genetic distinctions that separate one
species (chimpanzees) from another (humans). In
genomes involving billions of nucleotides, a tiny 2
percent difference translates into tens of millions of
ACGT differences. And that 2 percent difference
can be very broadly distributed. Humans and
chimps each have somewhere between 20,000 and
30,000 genes, so there are likely to be nucleotide
differences in every single gene.
D
What accounts for those differences? A few
years ago, the most ambitious project in the history
of biology was carried out: the sequencing of the
human genome. Then just four months ago, a team
of researchers reported that they had likewise
sequenced the complete chimpanzee genome.
Scientists have long known that chimps and humans
share about 98 percent of their DNA. At last, however, one can sit down with two scrolls of computer
To understand what distinguishes the DNA of
chimps and humans, one must first ask: What is a
gene? A gene is a string of nucleotides that specify
how a single distinctive protein should be made.
“The 2% Difference” Robert Sapolsky. Discover. April 2006, pp. 42–45. Reprinted by permission of the author.
1
2 The 2% Difference
Even if the same gene in chimps and humans differs
by an A here and a T there, the result may be of no
consequence. Many nucleotide differences are neutral—both the mutation and the normal gene cause
the same protein to be made. However, given the
right nucleotide difference between the same gene
in the two species, the resulting proteins may differ
slightly in construction and function.
One might assume that the differences between
chimp and human genes boil down to those sorts of
typographical errors: one nucleotide being swapped
for a different one and altering the gene it sits in.
But a close look at the two codebooks reveals very
few such instances. And the typos that do occasionally occur follow a compelling pattern. It’s important to note that genes don’t act alone. Yes, each
gene regulates the construction of a specific protein.
But what tells that gene when and where to build
that protein? Regulation is everything: It’s important not to start up genes related to puberty during,
say, infancy, or to activate genes that are related to
eye color in the bladder.
In the DNA code list, that critical information
is contained in a short stretch of As and Cs and Gs
and Ts that lie just before each gene and act as a
switch that turns the gene on or off. The switch, in
turn, is flicked on by proteins called transcription
factors, which activate certain genes in response to
certain stimuli. Naturally, every gene is not regulated by its own distinct transcription factor; otherwise, a codebook of as many as 30,000 genes would
require 30,000 transcription factors—and 30,000
more genes to code for them. Instead, one transcription factor can flick on an array of functionally
related genes. For example, a certain type of injury
can activate one transcription factor that turns on a
bunch of genes in your white blood cells, triggering
inflammation.
Accurate switch flickers are essential. Imagine
the consequences if some of those piddly nucleotide
changes arose in a protein that happened to be a
transcription factor: Suddenly, instead of activating
23 different genes, the protein might charge up 21
or 25 of them—or it might turn on the usual 23 but
in different ratios than normal. Suddenly, one minor
nucleotide difference would be amplified across a
network of gene differences. (And imagine the ramifications if the altered proteins are transcription
factors that activate the genes coding for still other
transcription factors!) When the chimp and human
genomes are compared, some of the clearest cases
of nucleotide differences are found in genes coding
for transcription factors. Those cases are few, but
they have far-ranging implications.
The genomes of chimps and humans reveal a
history of other kinds of differences as well. Instead
of a simple mutation, in which a single nucleotide is
copied incorrectly, consider an insertion mutation,
where an extra A, C, G, or T is dropped in, or a deletion mutation, whereby a nucleotide drops out.
Insertion or deletion mutations can have major consequences: Imagine the deletion mutation that turns
the sentence “I’ll have the mousse for dessert” into
“I’ll have the mouse for dessert,” or the insertion
mutation implicit in “She turned me down for a date
after I asked her to go boweling with me.”
Sometimes, more than a single nucleotide is
involved; whole stretches of a gene may be dropped
or added. In extreme cases, entire genes may be
deleted or added.
ore important than how the genetic changes
arise—by insertion, deletion, or straight mutation—is where in the genome they occur. Keep in
mind that, for these genetic changes to persist from
generation to generation, they must convey some
evolutionary advantage. When one examines the 2
percent difference between humans and chimps, the
genes in question turn out to be evolutionarily
important, if banal. For example, chimps have a
great many more genes related to olfaction than we
do; they’ve got a better sense of smell because
we’ve lost many of those genes. The 2 percent distinction also involves an unusually large fraction of
genes related to the immune system, parasite vulnerability, and infectious diseases: Chimps are
resistant to malaria, and we aren’t; we handle tuberculosis better than they do. Another important fraction of that 2 percent involves genes related to
reproduction—the sorts of anatomical differences
that split a species in two and keep them from interbreeding.
M
That all makes sense. Still, chimps and humans
have very different brains. So which are the brainspecific genes that have evolved in very different
directions in the two species? It turns out that there
are hardly any that fit that bill. This, too, makes a
great deal of sense. Examine a neuron from a human
brain under a microscope, then do the same with a
neuron from the brain of a chimp, a rat, a frog, or a
sea slug. The neurons all look the same: fibrous
dendrites at one end, an axonal cable at the other.
They all run on the same basic mechanism: chan-
The 2% Difference 3
nels and pumps that move sodium, potassium, and
calcium around, triggering a wave of excitation
called an action potential. They all have a similar
complement of neurotransmitters: serotonin,
dopamine, glutamate, and so on. They’re all the
same basic building blocks.
The main difference is in the sheer number of
neurons. The human brain has 100 million times the
number of neurons a sea slug’s brain has. Where do
those differences in quantity come from? At some
point in their development, all embryos—whether
human, chimp, rat, frog, or slug—must have a single first cell committed toward generating neurons.
That cell divides and gives rise to 2 cells; those
divide into 4, then 8, then 16. After a dozen rounds
of cell division, you’ve got roughly enough neurons
to run a slug. Go another 25 rounds or so and you’ve
got a human brain. Stop a couple of rounds short of
that and, at about one-third the size of a human
brain, you’ve got one for a chimp. Vastly different
outcomes, but relatively few genes regulate the
number of rounds of cell division in the nervous
system before calling a halt. And it’s precisely some
of those genes, the ones involved in neural development, that appear on the list of differences between
the chimp and human genomes.
That’s it; that’s the 2 percent solution. What’s
shocking is the simplicity of it. Humans, to be
human, don’t need to have evolved unique genes
that code for entirely novel types of neurons or neurotransmitters, or a more complex hippocampus
(with resulting improvements in memory), or a
more complex frontal cortex (from which we gain
the ability to postpone gratification). Instead, our
braininess as a species arises from having humongous numbers of just a few types of off-the-rack
neurons and from the exponentially greater number
of interactions between them. The difference is
sheer quantity: Qualitative distinctions emerge from
large numbers. Genes may have something to do
with that quantity, and thus with the complexity of
the quality that emerges. Yet no gene or genome can
ever tell us what sorts of qualities those will be.
Remember that when you and the chimp are eyeball
to eyeball, trying to make sense of why the other
seems vaguely familiar.